Helmholtz Gemeinschaft


The ClC-K2 chloride channel is critical for salt handling in the distal nephron

Item Type:Article
Title:The ClC-K2 chloride channel is critical for salt handling in the distal nephron
Creators Name:Hennings, J.C. and Andrini, O. and Picard, N. and Paulais, M. and Huebner, A.K. and Lopez Cayuqueo, I.K. and Bignon, Y. and Keck, M. and Cornière, N. and Böhm, D. and Jentsch, T.J. and Chambrey, R. and Teulon, J. and Hübner, C.A. and Eladari, D.
Abstract:Chloride transport by the renal tubule is critical for blood pressure (BP), acid-base, and potassium homeostasis. Chloride uptake from the urinary fluid is mediated by various apical transporters, whereas basolateral chloride exit is thought to be mediated by ClC-Ka/K1 and ClC-Kb/K2, two chloride channels from the ClC family, or by KCl cotransporters from the SLC12 gene family. Nevertheless, the localization and role of ClC-K channels is not fully resolved. Because inactivating mutations in ClC-Kb/K2 cause Bartter syndrome, a disease that mimics the effects of the loop diuretic furosemide, ClC-Kb/K2 is assumed to have a critical role in salt handling by the thick ascending limb. To dissect the role of this channel in detail, we generated a mouse model with a targeted disruption of the murine ortholog ClC-K2. Mutant mice developed a Bartter syndrome phenotype, characterized by renal salt loss, marked hypokalemia, and metabolic alkalosis. Patch-clamp analysis of tubules isolated from knockout (KO) mice suggested that ClC-K2 is the main basolateral chloride channel in the thick ascending limb and in the aldosterone-sensitive distal nephron. Accordingly, ClC-K2 KO mice did not exhibit the natriuretic response to furosemide and exhibited a severely blunted response to thiazide. We conclude that ClC-Kb/K2 is critical for salt absorption not only by the thick ascending limb, but also by the distal convoluted tubule.
Keywords:Chloride Channels, Bartter-s Syndrome, Ion Transport, Transgenic Mouse, Animals, Mice
Source:Journal of the American Society of Nephrology
Publisher:American Society of Nephrology
Page Range:209-217
Date:January 2017
Official Publication:https://doi.org/10.1681/ASN.2016010085
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library